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Retinal vasculopathy with cerebral leukodystrophy with systemic manifestations


Other Names:
Cerebroretinal vasculopathy, hereditary; CRV; Retinopathy, vascular, with cerebral and renal involvement and Raynaud and migraine phenomena; Cerebroretinal vasculopathy, hereditary; CRV; Retinopathy, vascular, with cerebral and renal involvement and Raynaud and migraine phenomena; RVCL; Autosomal Dominant Retinal Vasculopathy with Cerebral Leukodystrophy; ADRVCL; Retinal vasculopathy and cerebral leukoencephalopathy; RVCL-S See More
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Subtypes:
Retinal vasculopathy with cerebral leukodystrophy and systemic manifestations (RVCL-S) affects the small blood vessels in the central nervous system and other organs. Symptoms begin in adulthood and can include loss of vision, Raynaud's disease, kidney and liver disease, and cognitive problems that get worse over time. Other symptoms may include migraines, gastrointestinal bleeding, and hypothyroidism. Death often occurs 10-15 years after the first symptoms appear. RVCL-S is caused by genetic variations in the TREX1 gene, and is inherited in an autosomal dominant pattern. Diagnosis is based on the symptoms, clinical exam, imaging studies of the brain, and may be confirmed by the results of genetic testing. Treatment is focused on managing the symptoms.[1][2][3]

RVCL-S is considered to include the following three diseases which were previously thought to be separate conditions: hereditary endotheliopathy, retinopathy, nephropathy, and stroke (HERNS); cerebroretinal vasculopathy (CRV); and hereditary vascular retinopathy (HVR).[1]
Last updated: 9/29/2020
The following list includes the most common signs and symptoms in people with retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations (RVCL-S). These features may be different from person to person. Some people may have more symptoms than others and symptoms can range from mild to severe. This list does not include every symptom or feature that has been described in this condition.

Symptoms of RVCL-S may include:[1][2][3]
  • Vision problems due to retina damage (retinopathy)
  • Raynaud's disease
  • Kidney disease
  • Liver disease
  • Gastrointestinal bleeding
  • Hypertension
  • Cognitive problems
  • Psychiatric disorders
The first symptoms are Raynaud's disease and vision problems which may occur in the 20s. Vision problems tend to lead to blindness. Kidney and liver disease may occur in the 30s. Brain disease starts in the 40-50s. The symptoms of RVCL-S get worse over time, often leading to death in 10 to 15 years.[2][3]
Last updated: 9/29/2020

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

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Medical Terms Other Names
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HPO ID
80%-99% of people have these symptoms
Focal white matter lesions 0007042
Leukodystrophy 0002415
30%-79% of people have these symptoms
Abnormal retinal vascular morphology
Abnormality of retina blood vessels
0008046
Apraxia 0002186
Behavioral abnormality
Behavioral changes
Behavioral disorders
Behavioral disturbances
Behavioral problems
Behavioral/psychiatric abnormalities
Behavioural/Psychiatric abnormality
Psychiatric disorders
Psychiatric disturbances
[ more ] 		0000708
Dysarthria
Difficulty articulating speech
0001260
Hemiparesis
Weakness of one side of body
0001269
Mental deterioration
Cognitive decline
Cognitive decline, progressive
Intellectual deterioration
Progressive cognitive decline
[ more ] 		0001268
Migraine
Intermittent migraine headaches
Migraine headache
Migraine headaches
[ more ] 		0002076
Progressive visual loss
Progressive loss of vision
Progressive vision loss
Progressive visual impairment
Slowly progressive visual loss
Vision loss, progressive
Visual loss, progressive
[ more ] 		0000529
Retinopathy
Noninflammatory retina disease
0000488
Seizure 0001250
Stroke 0001297
5%-29% of people have these symptoms
Ataxia 0001251
Glomerulopathy 0100820
Hematuria
Blood in urine
0000790
Micronodular cirrhosis 0001413
Nephropathy 0000112
Proteinuria
High urine protein levels
Protein in urine
[ more ] 		0000093
Sensory impairment 0003474
Percent of people who have these symptoms is not available through HPO
Abnormality of the periventricular white matter 0002518
Adult onset
Symptoms begin in adulthood
0003581
Autosomal dominant inheritance 0000006
Central nervous system degeneration 0007009
Dementia
Dementia, progressive
Progressive dementia
[ more ] 		0000726
Diminished ability to concentrate
Poor concentration
0031987
Elevated erythrocyte sedimentation rate
High ESR
0003565
Elevated hepatic transaminase
High liver enzymes
0002910
Limb pain 0009763
Lower limb hyperreflexia
Overactive lower leg reflex
0002395
Macular edema 0040049
Progressive
Worsens with time
0003676
Progressive forgetfulness 0007017
Punctate vasculitis skin lesions 0200030
Raynaud phenomenon 0030880
Retinal exudate 0001147
Retinal hemorrhage
Retinal bleeding
0000573
Telangiectasia 0001009
Vasculitis in the skin 0200029
Visual impairment
Impaired vision
Loss of eyesight
Poor vision
[ more ] 		0000505
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Last updated: 11/1/2020
Retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations (RVCL-S) is caused by the TREX1 gene not working correctly. DNA changes known as pathogenic variants are responsible for making genes work incorrectly or sometimes, not at all.[1]
Last updated: 9/29/2020
Retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations (RVCL-S) is inherited in an autosomal dominant pattern.[1] All individuals inherit two copies of each gene. Autosomal means the gene is found on one of the numbered chromosomes found in both sexes. Dominant means that only one altered copy of a gene is necessary to have the condition. The alteration can be inherited from either parent. Sometimes an autosomal dominant condition occurs because of a new genetic alteration (de novo) and there is no history of this condition in the family.
  
Each child of an individual with an autosomal dominant condition has a 50% or 1 in 2 chance of inheriting the alteration and the condition. Typically, children who inherit a dominant alteration will have the condition, but they may be more or less severely affected than their parent. Sometimes a person may have a gene alteration for an autosomal dominant condition and show no signs or symptoms of the condition.

Last updated: 9/29/2020
Retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations (RVCL-S) is diagnosed based on the symptoms, clinical examination, and imaging studies of the brain. The diagnosis can be confirmed based on the results of genetic testing.[1][3]
Last updated: 9/29/2020

Testing Resources

  • The Genetic Testing Registry (GTR) provides information about the genetic tests for this condition. The intended audience for the GTR is health care providers and researchers. Patients and consumers with specific questions about a genetic test should contact a health care provider or a genetics professional.
Treatment of retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations (RVCL-S) is focused on managing the symptoms.

Specialists involved in the care of someone with RVCL-S may include:[1]
  • Ophthalmologist
  • Neurologist
  • Nephrologist
  • Liver specialist
  • Endocrinologist
  • Hematologist
  • Rheumatologist
Last updated: 9/29/2020
There are about 200 reports of people with retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations (RVCL-S) in the medical literature.[4] It is not known exactly how many people have this condition. 
Last updated: 9/29/2020

If you need medical advice, you can look for doctors or other healthcare professionals who have experience with this disease. You may find these specialists through advocacy organizations, clinical trials, or articles published in medical journals. You may also want to contact a university or tertiary medical center in your area, because these centers tend to see more complex cases and have the latest technology and treatments.

If you can’t find a specialist in your local area, try contacting national or international specialists. They may be able to refer you to someone they know through conferences or research efforts. Some specialists may be willing to consult with you or your local doctors over the phone or by email if you can't travel to them for care.

You can find more tips in our guide, How to Find a Disease Specialist. We also encourage you to explore the rest of this page to find resources that can help you find specialists.

Healthcare Resources

Research helps us better understand diseases and can lead to advances in diagnosis and treatment. This section provides resources to help you learn about medical research and ways to get involved.

Patient Registry

  • A registry supports research by collecting of information about patients that share something in common, such as being diagnosed with Retinal vasculopathy with cerebral leukodystrophy with systemic manifestations. The type of data collected can vary from registry to registry and is based on the goals and purpose of that registry. Some registries collect contact information while others collect more detailed medical information. Learn more about registries.

    Registries for Retinal vasculopathy with cerebral leukodystrophy with systemic manifestations:
    Myelin Disorders Bioregistry Project
     

Support and advocacy groups can help you connect with other patients and families, and they can provide valuable services. Many develop patient-centered information and are the driving force behind research for better treatments and possible cures. They can direct you to research, resources, and services. Many organizations also have experts who serve as medical advisors or provide lists of doctors/clinics. Visit the group’s website or contact them to learn about the services they offer. Inclusion on this list is not an endorsement by GARD.

Organizations Supporting this Disease

Organizations Providing General Support

These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

Where to Start

  • MedlinePlus Genetics contains information on Retinal vasculopathy with cerebral leukodystrophy with systemic manifestations. This website is maintained by the National Library of Medicine.

In-Depth Information

  • The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
  • Online Mendelian Inheritance in Man (OMIM) is a catalog of human genes and genetic disorders. Each entry has a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine. 
  • Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.
  • PubMed is a searchable database of medical literature and lists journal articles that discuss Retinal vasculopathy with cerebral leukodystrophy with systemic manifestations. Click on the link to view a sample search on this topic.

Questions sent to GARD may be posted here if the information could be helpful to others. We remove all identifying information when posting a question to protect your privacy. If you do not want your question posted, please let us know.

  1. de Boer I, Pelzer N, Terwindt G. Retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations. GeneReviews. Updated Sept 19, 2020; https://www.ncbi.nlm.nih.gov/books/NBK546576.
  2. Pelzer N, Hoogeveen ES, Haan J, Bunnik R, Poot CC, et al. Systemic features of retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations: a monogenic small vessel disease.. J Intern Med. Mar 2019; 285(3):317-332. https://pubmed.ncbi.nlm.nih.gov/30411414.
  3. Stam AH, Kothari PH, Shaikh A, Gschwendter A, Jen JC, et al. Retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations. Brain. Nov. 1, 2016; 139(11):2902-2922. https://pubmed.ncbi.nlm.nih.gov/27604306.
  4. Ford AL, Chin VW, Fellah S, Binkley MM, Bodin AM, et al. Lesion evolution and neurodegeneration in RVCL-S: A monogenic microvasculopathy. Neurology. Sep 2020; 4:10. https://pubmed.ncbi.nlm.nih.gov/32887784.